TY - JOUR
T1 - Limited sampling strategies for individualized BAX 855 prophylaxis in severe hemophilia A
T2 - in silico evaluation
AU - Bukkems, Laura H.
AU - OPTI-CLOT study group, SYMPHONY consortium
AU - Goedhart, Tine M. H. J.
AU - Zwaan, C. Michel
AU - Cnossen, Marjon H.
AU - Mathôt, Ron A. A.
N1 - Funding Information: Funding and acknowledgments: This study was performed as part of the OPTI-CLOT international multicenter research consortium, ‘Patient tailOred PharmacokineTIc-guided dosing of CLOTting factor concentrates and desmopressin in bleeding disorders,’ which is currently WP6 within the SYMPHONY consortium. L.H.B. and M.H.J.G. are funded by the SYMPHONY consortium. The SYMPHONY consortium aims to orchestrate personalized treatment in patients with bleeding disorders, and is a unique collaboration between patients, healthcare professionals and translational & fundamental researchers specialized in inherited bleeding disorders, as well as experts from multiple disciplines. It aims to identify best treatment choice for each individual based on bleeding phenotype. In order to achieve this goal, work packages have been organized according to three themes e.g. Diagnostics (workpackage 3&4); Treatment (workpackages 5–9) and Fundamental Research (workpackages 10–12). This research received funding from the Netherlands Organization for Scientific Research (NWO) in the framework of the NWA-ORC Call grant agreement NWA.1160.18.038. Principal investigator: Dr M.H. Cnossen; project coordinator: Dr S.H. Reitsma. Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/4/1
Y1 - 2023/4/1
N2 - OBJECTIVE: Limited sampling strategies (LSS) lower the burden of pharmacokinetic (PK)-guided dosing, but an extensive evaluation of LSS for BAX 855 (Adynovi) is currently lacking. This study aimed to develop a LSS for BAX 855 and combine this with a LSS of a standard half-life (SHL) factor VIII (FVIII) concentrate in a clinical setting. METHODS: Individual PK parameters of BAX 855 were estimated for 10 000 virtual patients with severe hemophilia A using Monte Carlo simulations. Several LSS consisting of 2-6 samples were examined based on patient burden, bias and accuracy of clearance, elimination half-life, volume of distribution and trough levels at 72 h (C72). Analyses were performed separately for adults and children <12 years. RESULTS: The preferred LSS for BAX 855 consisted of three sampling points at 15-30 min, 48 h and 72 h for both adults (mean accuracy C72: 14.0% vs. 10.8% using six samples) and children (mean accuracy C72: 14.9% vs. 11.4% using six samples). The best strategy with two samples (peak, 48 h) resulted in an adequate, but lower accuracy than strategies with ≥3 samples (mean accuracy C72: 22.3%). The optimal combination of the LSS of SHL FVIII and BAX 855 led to six samples during four clinical visits. CONCLUSION: This in silico study has identified that two to three samples are necessary to estimate the individual PK of BAX-855 adequately. These samples can be collected in one or two clinical visits. When combining PK profiling of SHL FVIII and BAX 855, six samples during four clinical visits are needed.
AB - OBJECTIVE: Limited sampling strategies (LSS) lower the burden of pharmacokinetic (PK)-guided dosing, but an extensive evaluation of LSS for BAX 855 (Adynovi) is currently lacking. This study aimed to develop a LSS for BAX 855 and combine this with a LSS of a standard half-life (SHL) factor VIII (FVIII) concentrate in a clinical setting. METHODS: Individual PK parameters of BAX 855 were estimated for 10 000 virtual patients with severe hemophilia A using Monte Carlo simulations. Several LSS consisting of 2-6 samples were examined based on patient burden, bias and accuracy of clearance, elimination half-life, volume of distribution and trough levels at 72 h (C72). Analyses were performed separately for adults and children <12 years. RESULTS: The preferred LSS for BAX 855 consisted of three sampling points at 15-30 min, 48 h and 72 h for both adults (mean accuracy C72: 14.0% vs. 10.8% using six samples) and children (mean accuracy C72: 14.9% vs. 11.4% using six samples). The best strategy with two samples (peak, 48 h) resulted in an adequate, but lower accuracy than strategies with ≥3 samples (mean accuracy C72: 22.3%). The optimal combination of the LSS of SHL FVIII and BAX 855 led to six samples during four clinical visits. CONCLUSION: This in silico study has identified that two to three samples are necessary to estimate the individual PK of BAX-855 adequately. These samples can be collected in one or two clinical visits. When combining PK profiling of SHL FVIII and BAX 855, six samples during four clinical visits are needed.
KW - extended half-life
KW - factor VIII
KW - hemophilia A
KW - limited sampling strategy
KW - pharmacokinetics
UR - http://www.scopus.com/inward/record.url?scp=85152110760&partnerID=8YFLogxK
U2 - https://doi.org/10.1097/MBC.0000000000001204
DO - https://doi.org/10.1097/MBC.0000000000001204
M3 - Article
C2 - 37038844
SN - 0957-5235
VL - 34
SP - 171
EP - 178
JO - Blood coagulation & fibrinolysis
JF - Blood coagulation & fibrinolysis
IS - 3
ER -